Human exploration of space requires an understanding of the risks to which crews will be exposed during such missions, and the mitigation of those risks to the fullest extent practical. This becomes a greater imperative as we prepare for interplanetary expeditions involving long periods in weightlessness in transit to and then from the destination (a planet, such as Mars, or perhaps a point in space, such as the Lagrangian point L2), and exposure to the unique environment of the destination itself. We need to know, more definitively, what the risks are to human health, safety, and performance, and how to prevent or counteract them throughout all phases of a long duration mission. The Johnson Space Center's Space and Life Sciences Directorate and the National Space Biomedical Research Institute (NSBRI) have implemented an effort to identify the most critical risks confronting humans on such mission and the types of research and technology efforts required to mitigate and otherwise reduce the probability and severity of those risks. This paper describes the "Critical Path Roadmap Project" to define, assess and prioritize the risks and present the results of the assessment with an emphasis on the research and technology priorities to meet the challenge of long duration human spaceflight mission.